Obstructive sleep apnea aggravates neuroinflammation and pyroptosis in early brain injury following subarachnoid hemorrhage via ASC/HIF-1α pathway

Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

Effects of Ticagrelor on oxidative stress, coagulation function, platelet function and related factors in patients with coronary artery disease undergoing interventional therapy

Objective: To explore the effects of Ticagrelor on oxidative stress, coagulation function, platelet function and related factors in patients with coronary artery disease undergoing interventional therapy. Methods: A total of 140 patients with coronary artery disease who underwent percutaneous coronary intervention in our hospital from October 2016 to March 2018 were selected as the study subjects and were divided into control group (70 cases) and observation group (70 cases) by drawing lots. Both groups were treated with symptomatic routine therapy before operation. On this basis, the control group was treated with clopidogrel before operation, and the observation group was treated with Ticagrelor before operation on the basis of routine treatment. The changes of oxidative stress, coagulation index, platelet function and related factors were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences in oxidative stress factors, coagulation parameters, platelet parameters and related factors factors between the two groups. After treatment, the levels of MDA, MPAR, VEGF and MMP-9 in the two groups were lower than those before treatment, while the levels of SOD, APTT, TT and PT were higher than those before treatment;and the levels of MDA, MPAR, VEGF, MMP-9, APTT and PT in the observation group were significantly lower than those in the control group after treatment, while the levels fo SOD, TT and IPA in the observation group were significantly higher than those in the control group. Conclusions: Ticagrelor can better reduce oxidative stress injury, improve coagulation function and coronary stenosis, and inhibit platelet aggregation in patients with coronary heart disease undergoing PCI than clopidogrel. It has clinical popularization significance.